In attempting to cultivate adult pancreatic islet cells, the objective has long been to isolate pancreatic progenitor cells that are capable of proliferation and differentiation into pancreatic β cells. One important step in isolation of pancreatic progenitor cells would be to identify recognizable cell markers, specific for the progenitor cells. Both intracellular and extracellular markers have been investigated for this purpose.
Once identified, extracellular markers would offer the advantage that the cells expressing the marker can be sorted under sterile conditions and kept alive to continue their study. Epithelial cell adhesion molecules such as Ep-CAM and integrins have been investigated as pancreatic islet progenitor markers. See e.g., Cirulli et al., J. Cell Biol. 140:1519-1534 (1998); and Cirulli et al., J. Cell Biol. 150:1445-1460 (2000). Cells selected by these makers have been shown to express transcription factors, such as PDX-1, indicating that they belong to the cell lineage in pancreatic development. However those cells have not been shown to be able to produce endocrine hormones such as insulin. Id.
Intracellular markers, particularly those from embryonic cells that develop into mature islet cells, have been extensively studied as progenitor markers. Transcription factors such as PDX-1, Ngn3, and Hlxb9, for example, have been studied. They are expressed in cells that are programmed during embryonic development to become pancreatic endocrine cells. However, these intracellular markers offer less practical value than extracellular makers in selecting progenitor cells, because analysis of expression of those markers requires either the killing the cells or permanent modification of the cells by genetic engineering of reporter genes into the cells.
Thus, there is a great need to identify extracellular marker(s) that allow the identification and selection of human adult pancreatic endocrine progenitor cells. The present invention solves this and other problems.